Insulin Resistance: the Vascular Scene
The VASCULAR Scene
Normally insulin produces nitric oxide dependent vasodilatation of the peripheral resistance vessels. Am J Physiol. 1994 Aug;267(2 Pt 1):E187-202 Endothelium dependent vasodilatation has been shown to be defective in insulin resistant states. Eur J Clin Invest. 2001 Dec;31(12):1013-4. Hyperinsulinism which characterises insulin resistance is thought to produce vascular damage with predilection for atherosclerosis though induction of vascular smooth muscle proliferation. The hyperinsulinism of insulin resistance stimulates the MAP kinase pathway excessively, resulting in increased growth and proliferation of vascular smooth muscle cells, with increased collagen formation and release of growth and chemotactic factors which facilitate atherosclerosis. Lowering of hyperinsulinaemia using modalities as metformin would thus be expected to improve atherosclerosis related macrovascular disease as opposed to exogenous insulin or insulin secretagogue therapies, as demonstrated in the UKPDS trial. Lancet. 1998 Sep 12;352(9131):854-65. Insulin normally decreases vagal tone while increasing sympathetic drive, and hence hyperinsulinism might contribute to the increased sympathetic drive seen in insulin-resistant obese J Clin Invest.1994 Jun;93(6):2365-71. or perhaps not? J Clin Endocrinol Metab. 2001 Mar;86(3):1403-9
Normally insulin produces nitric oxide dependent vasodilatation of the peripheral resistance vessels. Am J Physiol. 1994 Aug;267(2 Pt 1):E187-202 Endothelium dependent vasodilatation has been shown to be defective in insulin resistant states. Eur J Clin Invest. 2001 Dec;31(12):1013-4. Hyperinsulinism which characterises insulin resistance is thought to produce vascular damage with predilection for atherosclerosis though induction of vascular smooth muscle proliferation. The hyperinsulinism of insulin resistance stimulates the MAP kinase pathway excessively, resulting in increased growth and proliferation of vascular smooth muscle cells, with increased collagen formation and release of growth and chemotactic factors which facilitate atherosclerosis. Lowering of hyperinsulinaemia using modalities as metformin would thus be expected to improve atherosclerosis related macrovascular disease as opposed to exogenous insulin or insulin secretagogue therapies, as demonstrated in the UKPDS trial. Lancet. 1998 Sep 12;352(9131):854-65. Insulin normally decreases vagal tone while increasing sympathetic drive, and hence hyperinsulinism might contribute to the increased sympathetic drive seen in insulin-resistant obese J Clin Invest.1994 Jun;93(6):2365-71. or perhaps not? J Clin Endocrinol Metab. 2001 Mar;86(3):1403-9